W. Cutting

Therapeutic activity of narcissus alkaloid on Rauscher leukemia and comparison with standard drugs.

Summary An alkaloid (2-X), tentatively identified as pseudolycorine, has been isolated from Narcissus tazetta L. This alkaloid, primarily studied as a new antiviral agent derived from the screening of medicinal plants of the Pacific area, has been shown to exert a superior prolongation effect on the life span of established Rauscher leukemic mice having palpable splenomegaly, in comparison with standard antileukemic drugs. It was found that the alkaloid suppressed the development of splenomegaly and the increase in number of nucleated blood cells, and dropped the virus titer in plasma without apparent toxicity. A second alkaloidal complex, called residual alkaloid, also showed remarkable antileukemic activity.

Antiviral Principles of Propionibacteria-Isolation and Activity of Propionins B and C

Summary Further purification of propionin, an antiviral agent active against Columbia SK virus infections in mice, from cellular extracts of Propionibacterium freudenreichii by dialysis, paper chromatography and gel filtration on Sephadex is described. The active agent is shown to be a mixture of two substances, referred to as propionins B and C and a method of obtaining a fraction rich in these two substances, essentially by gel filtration on Sephadex is also described. Some preliminary data on the probable molecular size and chemical nature is also presented.

Effect of Long-Term Administration of Narcissus Alkaloid on Rauscher Leukemia and Combinations with Standard Drugs

Summary Long-term treatment with narcissus alkaloid (pseudolycorine or the residual alkaloid) at well tolerated doses was remarkably effective against established Rauscher leukemic mice, in comparison with standard antileukemic drugs. Combination of narcissus alkaloid with cyclophosphamide or 6-MP was more effective than the single administration of either drug, while combination with vincristine or interferon inducers (poly I:C or tilorone HCl) did not increase the effect. Narcissus alkaloid did not impair humoral antibody production in the leukemic mice, while the standard drugs were immunosuppressive during long-term administration. Also, narcissus alkaloid did not suppress interferon induction (by poly I:C) in leukemic mice. We thank Dr. M. A. Chirigos, NIH, for supplying Rauscher virus, antiviral testing by XC cell assay, and helpful advice; and Dr. P. A. Tavormina, Mead Johnson Res. Center, for supplying cyclophosphamide (Cytoxan).

Antiviral Activity of Higher Plants and Propionin on Lymphocytic Choriomeningitis Infection

Summary Further studies of 2 higher plants (Narcissus tazetta L and Magnolia kobus DC) with antiviral action against lymphocytic choriomeningitis infection in mice have been reported, and the activity of a third substance, propionin, added. The anti-LCM activities of the 3 natural products have been compared with methotrexate. The authors are indebted to Dr. H. A. Chirigos, Nat. Inst. of Health, for supplying methotrexate and to Dr. Ralph F. Anderson, International Minerals & Chemical Corp., for supplying crudes containing propionin.

THE HIGHER PLANTS WITH ANTIVIRAL AND ANTI‐LETHAL ACTIVITY ON VIRUS INFECTIONS IN MICE. *

The d i f f i c u l t y i n f ind ing a c t i v e the rapeu t i c drugs of s y n t h e t i c o r i g i n f o r neu ro t rop ic RNA v i r u s i n f e c t i o n s a t t h e animal l e v e l has l ed us t o r e sea rch i n t h e f i e l d of n a t u r a l products. a n t i v i r a l s c reen ing i n Japanese-Chinese m e a c i n a l p l a n t s has been seria l l y reported. l -6 Narcissus tazetta (H6727) and Sambucus s i ebo ld iana (H7443), which showed remarkable a c t i v i t y i n reducing m o r t a l i t y i n bo th ColumbiaSK (Col SK) and lymphocytic choriomeningi t is (LCM) v i r u s i n f e c t i o n s i n mice. The progress of t h i s

Purification of Propionin, an Antiviral Agent from Propionibacteria

Summary A potent antiviral agent, pro-pionin, active against Col. SK virus infections in mice, has been isolated from cellular extracts of Propionibacterium freudenreichii. Partial purification of propionin by organic solvents, Sephadex and paper chroma tography has been achieved. Preliminary identification has been carried out and the available data indicate propionin to be peptide in nature.

Antiviral Activity of Higher Plants on Lymphocytic Choriomeningitis Infection in vitro and in vivo.

Summary Two higher plants (Magnolia kobus DC. and Narcissus tazetta L.) have emerged from a screening program of Chinese medicinal agents as antiviral drugs against lymphocytic choriomeningitis infection in mice.

Propionin B, an Antiviral Principle of Propionibacteria

A fraction, containing propionins B and C, which was active against Columbia SK virus has now been shown to be active against EMC virus in mice. From this mixture, a chromatographically homogenous sub

COMPLETE CURE OF DNA VIRUS INFECTION IN CULTURED CELLS BY DRUG COMBINATIONS.

Summary Complete eradication of vaccinia virus and recovery of normal cells from the infected cultures of HeLa cells by treatment with drug combinations has been described. Combinations of 5-methyltryptophan and 5-bromodeoxyuridine or noformicin and 5-bromodeoxyuridine, which kept cultures nearly static without increase or decrease of cell population, were most adequate for this purpose. The recovered cells showed no immunity against vaccinia reinfection. Single drug administration could not eradicate the virus and could not save the infected cultures from final death. The eradication activity of the combination was doubtful against adeno type 12 virus.

Antiviral Activity of Tobacco Leaf on Encephalomyocarditis (EMC) Virus Infection

Summary A water-soluble and athanol-insoluble fraction of tobacco leaf of cigarettes has been found to have antiviral activity against EMC virus infection in mice and tissue cultures, and antilethal activity on LCM virus infection in mice. This activity was compared with poly I:C and tilorone as standard agents. The lower molecular portion of the tobacco extract inhibited the single cycle of EMC virus reproduction in KB cells even when it was added 2 hr after infection. It also inhibited the cytopathic effects of vesicular stomatitis, polio type 2, reo type 2, and vaccinia viruses, but not adeno type 12, in KB cells. The higher molecular portion showed no antiviral activity in KB cells, although it showed activity in mice against EMC infection. Although both the lower and higher molecular portions of tobacco extract protected mice from EMC paralysis after a single pre-treatment, neither induced serum interferon.